ABSTRACT: The use of benzodiazepines to control agitation in delirium in the last days of life is controversial.To compare the effect of lorazepam vs placebo as an adjuvant to haloperidol for persistent agitation in patients with delirium in the setting of advanced cancer.Single-center, double-blind, parallel-group, randomized clinical trial conducted at an acute palliative care unit at MD Anderson Cancer Center, Texas, enrolling 93 patients with advanced cancer and agitated delirium despite scheduled haloperidol from February 11, 2014, to June 30, 2016, with data collection completed in October 2016.Lorazepam (3 mg) intravenously (n?=?47) or placebo (n?=?43) in addition to haloperidol (2 mg) intravenously upon the onset of an agitation episode.The primary outcome was change in Richmond Agitation-Sedation Scale (RASS) score (range, -5 [unarousable] to 4 [very agitated or combative]) from baseline to 8 hours after treatment administration. Secondary end points were rescue neuroleptic use, delirium recall, comfort (perceived by caregivers and nurses), communication capacity, delirium severity, adverse effects, discharge outcomes, and overall survival.Among 90 randomized patients (mean age, 62 years; women, 42 [47%]), 58 (64%) received the study medication and 52 (90%) completed the trial. Lorazepam?+?haloperidol resulted in a significantly greater reduction of RASS score at 8 hours (-4.1 points) than placebo?+?haloperidol (-2.3 points) (mean difference, -1.9 points [95% CI, -2.8 to -0.9]; P?